Advanced and Metastatic Breast CancerPhase 1PASTORNCT02599714
Study of AZD2014 and Palbociclib in Patients With Estrogen Receptor Positive (ER+) Metastatic Breast Cancer
A Phase 1 study testing AZD2014, Palbociclib and Fulvestrant in people with Advanced and Metastatic Breast Cancer, run by AstraZeneca at 7 sites in 2 countries.
Trial summary
This dose finding/extension study was designed originally to consist of three parts: Part A was intended to identify the MTD of the AZD2014/ palbociclib combination on a background of fulvestrant (referred to as the triplet) in postmenopausal women with locally advanced/ metastatic estrogen receptor positive (ER+)… Read more about this study
- Who is it for?
- Ages 18 to 130 years, women only
- Conditions the study is for
- Advanced and Metastatic Breast Cancer
- What is being tested?
- AZD2014, Palbociclib and Fulvestrant
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 7 Dec 2015to 23 Nov 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed and dated written informed consent prior to any mandatory study specific procedures, sampling and analyses.
- Signed and dated written informed consent for tumour biopsies. If the tumour is found not to be safely accessible the biopsy will not be taken. Accessible lesions are defined as those which are biopsiable and amenable to repeat biopsy, unless clinically contraindicated. In this case the patient will remain in the study and there will be no penalty or loss of benefit to the patient and they will not be excluded from other aspects of the study.
- Postmenopausal women aged ≥ 18 years
- Negative pregnancy test prior to dosing and willing to use a highly effective method of contraception for the duration of the study and for 90 days after the last dose of IP if they are under 50 unless they have medically confirmed irreversible premature ovarian failure, bilateral oophorectomy, bilateral salpinectomy, or complete or partial hysterectomy.
- Highly effective methods of contraception are:
- Use of oral, injected or implanted hormonal methods of contraception which inhibit ovulation, either estrogen and progestogen containing intravaginal, transdermal) or only progesterone containing (oral, injectable, implantable)
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- Placement of an intrauterine device (IUD or intrauterine system (IUS)
- True abstinence
- Bilateral tubal ligation
- Vasectomised partner
- World Health Organisation/Eastern Cooperative Oncology Group (ECOG) performance status of patient is 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks.
- Histologically or cytologically proven diagnosis of breast cancer with evidence of locally advanced or metastatic disease, not amenable to resection or radiation therapy with curative intent.
- Documentation of estrogen receptor positive (ER+) breast cancer based on most recent tumour biopsy (unless bone-only disease).
- Documented human epidermal growth factor receptor 2 negative (HER2-) tumor on most recent tumor biopsy.
- Where regionally permitted, all patients must agree to provide if available a formalin-fixed paraffin embedded (FFPE) tissue biopsy sample taken at the time of presentation with recurrent or metastatic disease.
- At least one lesion (measurable and/or non measurable) that can be accurately assessed at baseline with computerised tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements.
- Meet the following study part specific criteria related to previous therapy for breast cancer:
- For Part A: Postmenopausal patient suitable for fulvestrant. Patient is allowed to have a maximum of 3 prior lines of chemotherapy. Previous treatment with CDK4/6 inhibitors is allowed
- For Part B: Postmenopausal patient with locally advanced or metastatic ER+ve breast cancer and refractory to AIs defined as:
- Disease recurrence while on, or within 12 months of end of adjuvant treatment with letrozole, anastrozole, or exemestane, or
- Disease progression while on, or within one month of end of letrozole, anastrozole or exemestane treatment for locally advanced or metastatic breast cancer
- Letrozole or anastrozole do not have to be the last treatment prior to randomization.
- Patients who received one prior chemotherapy line for advanced/metastatic breast cancer are allowed.
- Previous treatment with fulvestrant (or letrozole) is allowed. Other prior anticancer therapy (e.g. tamoxifen) are also allowed.
- For inclusion in the optional research component:
- Genetic research: Provision of signed and dated written consent for genetic research sampling and analyses. If a patient declines to participate in genetic component of the study, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent to the main study.
Who cannot join
- Prior chemotherapy, biological therapy, radiation therapy, or immunotherapy, androgens, thalidomide, other anticancer agents, investigational drug or corticosteroids within 14 days. Patients who received prior radiotherapy to >= 25% of bone marrow are not eligible independent of when it was received. Patients is not eligible if there are unresolved toxicities from prior therapy > CTCAE grade 1 at the start of study treatment with the exception of alopecia.
- Exposure to potent or moderate inhibitors or inducers of CYP3A4/5, Pgp (MDR1) or BCRP within stated washout periods.
- Exposure to sensitive or narrow therapeutic range substrates of drug transporters OATP1B1, OATP1B3, MATE1 and MATE2K within wash-out period (5 x elimination half-life).
- 4 Exposure to proton pump inhibitors within wash-out period (5 x elimination half-life).
- 5. Previous AZD2014, AZD8055 or other dual mTORC1/2 inhibitor
- In Part B only: Prior treatment with CDK4/6, or everolimus or any PI3K-mTOR pathway
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- 6. Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease. Patients with a history of CNS metastases or cord compression are eligible if definitively treated and clinically stable and off anticonvulsants and steroids for at least 4 weeks. Patients are not eligible if there is spinal cord compression and/or brain metastases, unless asymptomatic or treated and stable and off steroids for at least 4 weeks.
- 7. Evidence of severe or uncontrolled systemic diseases such as:
- Severe hepatic impairment
- Interstitial lung disease (bilateral, diffuse, parenchymal lung disease)
- Current unstable or uncompensated respiratory or cardiac conditions
- Uncontrolled hypertension
- Active bleeding diatheses
- Any active infection
- 8. Other malignancy within 3 years, except adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix
- 9. Experienced any of the following currently or in the last 12 months:
- Coronary/peripheral artery bypass graft
- Angioplasty
- Vascular stent
- Myocardial infarction
- Angina pectoris
- Congestive heart failure NYHA Grade ≥ 2
- Ventricular arrhythmias requiring continuous therapy
- Supraventricular arrhythmias including atrial fibrillation of any grade
- Symptomatic pulmonary embolism
- Haemorrhagic or thrombotic stroke
- 10. Abnormal ECHO or MUGA at baseline (LVEF <50%).
- 11. Mean resting QTc >470 msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes within 12 months.
- 12. Clinically important abnormalities in rhythm, conduction or morphology of resting ECG.
- 13. Hepatitis B (HBV), Hepatitis C (HCV) or Human Immunodeficiency virus (HIV).
- 14. Concomitant medications known to predispose to Torsade de Pointes, or factors that increase the risk of QT prolongation or risk of arrhythmic events such as:
- Heart failure
- Hypokalaemia
- Congenital long QT syndrome
- Family history of long QT syndrome
- Family history of unexplained sudden death under 40 years-of-age
- 15. Inadequate bone marrow reserve or organ function as demonstrated by:
- ANC <1.5 x 10^9/L.
- In Part A only - Cohorts of patients with specific baseline ANC range to be enrolled defined as follows: I) Low ANC patients: between 1.5 x 10^9/L and 3.0 x 10^9/L; ii) High ANC patients > 3.0 x 10^9/L.
- Platelets <100 x 10^9/L
- Haemoglobin <90 g/L
- ALT >2.5 x ULN or > 5 x ULN in the presence of liver mets.
- AST >2.5 x ULN or > 5 x ULN in the presence of liver mets.
- Total bilirubin >1.5 x ULN. Total bilirubin >3 x ULN in patients with documented Gilbert's Syndrome.
- Serum creatinine >1.5 x ULN concurrent with creatinine clearance ≤50 mL/min.
- 16. Pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome or Renal tubular acidosis.
- 17. Refractory nausea/vomiting, chronic GI diseases, inability to swallow the product or previous significant bowel resection.
- 18. Hypersensitivity to excipients of AZD2014, Palbociclib or Fulvestrant or drugs with a similar structure.
- 19. Diabetes Type I or uncontrolled Type II, as defined in WHO 2006 (fasting serum glucose of > 7.0 mmol/L [126 mg/dL]).
- 20. Patient with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term including patients with massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and over 50% of liver involvement in metastases.
- 21. Prior hematopoietic stem cell or bone marrow transplant.
- 22. Regular coumadin therapy. Low-molecular-weight heparin therapy or oral Factor Xa antagonists are allowed.
- 23. Known abnormalities in coagulation, e.g. bleeding diathesis.
- 24. Hematopoietic growth factors (such as erythropoietin, granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony stimulating factor [GM-CSF]) within 2 weeks prior. Primary prophylactic use of G-CSF is not permitted.
- 25. Other severe acute or chronic psychiatric condition that may increase the risks associated with study participation.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States5 sites
Research Site
Detroit, Michigan, 48201
Research Site
Encinitas, California, 92024
Research Site
Milwaukee, Wisconsin, 53226
Research Site
Nashville, Tennessee, 37203
Research Site
Sarasota, Florida, 34232
United Kingdom2 sites
Research Site
Liverpool, L7 8XP
Research Site
London, W1G 6AD
About this study
Official title: A Phase I/II Multicenter Study of the Combination of AZD2014 and Palbociclib on a Background of Hormonal Therapy in Patients With Locally Advanced/Metastatic Estrogen Receptor Positive Breast Cancer Comprising a Safety, Pharmacokinetic and Preliminary Efficacy Evaluation Followed by a Randomized, Double-Blind, Placebo-controlled, Parallel Group Extension (PASTOR).
This dose finding/extension study was designed originally to consist of three parts: Part A was intended to identify the MTD of the AZD2014/ palbociclib combination on a background of fulvestrant (referred to as the triplet) in postmenopausal women with locally advanced/ metastatic estrogen receptor positive (ER+) breast cancer. Part B was to further characterize safety, tolerability, PK, and preliminary efficacy in single-arm dose expansion groups. Part C was to be a Phase 2, randomized, double-blind, extension comparing the triplet and doublet combinations. Part C was deleted from the protocol and was not performed.
Read the detailed description
This dose finding/extension study was designed originally to consist of three parts:
Part A is a Phase 1 triplet-dose finding investigation in 3-6 patients per cohort to determine the maximum tolerated dose (MTD) of the triplet.
Part B is a single arm expansion in approximately 27 patients evaluable for response to define the recommended Phase 2 dose (RP2D).
Part C was intended to investigate the efficacy of the triplet combination at the RP2D in a randomized, double-blind, placebo-controlled, stratified, parallel group extension. Part C was intended to include ER+, locally advanced and/or metastatic breast cancer patients who have progressed following prior non-steroidal aromatase inhibitor (NSAI) endocrine therapy. Patients in Part C were to be randomized to receive either the triplet combination (AZD2014 + palbociclib + fulvestrant) or the doublet (matching AZD2014 placebo + palbociclib + fulvestrant). Patients were to be stratified according to hormone sensitivity, presence of visceral metastases, and prior CDK inhibitor treatment. Part C would have been conducted if indicated by the emerging data.
- Conditions
- Advanced and Metastatic Breast Cancer
- Being tested
- AZD2014, Palbociclib, Fulvestrant
- Keywords
- AZD2014, Palbociclib, Fulvestrant, Hormonal Therapy, Estrogen Receptor Positive, Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD2014Drug
Also called vistusertib
The triplet combination will be comprised of AZD2014 + palbociclib + fulvestrant.
PalbociclibDrug
Also called Ibrance, PD-0332991
cyclin dependent kinase inhibitor
FulvestrantDrug
Also called Faslodex
Fulvestrant hormonal therapy as background
| Study group | Role | What they receive |
|---|---|---|
| Triplet Combination (Dose Finding) | Experimental | Phase 1 triplet dose finding phase in 3-6 patients per cohort - approximately 30 patients depending on emerging data to determine the maximum tolerated dose (MTD) of the triplet. Receives: Drug: AZD2014; Drug: Palbociclib; Drug: Fulvestrant |
| Triplet Combination (Dose Expansion) | Experimental | Additional patients will be enrolled at the dose determined in Part A. Receives: Drug: AZD2014; Drug: Palbociclib; Drug: Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parts A and B: Number of adverse events experienced by patients
Safety and tolerability assessed through the incidence of adverse events.
Measured: Approximately 16 months
Secondary outcomes (15)
Part B: Progression Free Survival (PFS)
PFS assessed through change in tumour size (as well as assessment of non-target lesions and appearance of any new lesions) according to RECIST 1.1 criteria by Investigator assessment.
Measured: Assessed every 8 weeks for approximately 16 months
Parts A and B: Best Objective Response (BOR)
BOR assessed according to RECIST 1.1 criteria by Investigator assessment.
Measured: Assessed every 8 weeks for approximately 16 months
Parts A and B: Objective Response Rate (ORR)
ORR assessed through the number of patients who achieve a disease response (i.e. complete response or partial response) according to RECIST 1.1 criteria
Measured: Assessed every 8 weeks for approximately 16 months
Part B: Duration of Response (DoR)
DoR assessed as the time between disease response being achieved and progressive disease as assessed by RECIST 1.1 criteria or end of life (in the absence of progression)
Measured: Assessed every 8 weeks for approximately 16 months
Part B: Overall Survival (OS)
The time from start of treatment until end of life from any cause.
Measured: Approximately 24 months
Part A: Peak plasma concentrations (Cmax) of AZD2014 and palbociclib following single dose
Venous blood samples for determination of concentrations of AZD2014 and palbociclib in plasma will be collected.
Measured: Samples for single dose PK will be collected at prespecified time points up to 12 hours following dosing.
Parts A and B: Peak plasma concentrations (Cmax) of AZD2014 and palbociclib following multiple doses
Venous blood samples (2 mL for each drug) for determination of concentrations of AZD2014 and palbociclib in plasma will be collected.
Measured: Samples will be collected at prespecified time points up to 12 hours following dosing.
Parts A and B: Change from baseline in biomarker H-score
For those subjects with paired tumour biopsies the pharmacodynamic markers will be assessed by immunohistochemistry.
Measured: 16 months
Time to reach peak plasma concentrations (tmax) for AZD 2014 and palbociclib.
The plasma concentrations of AZD2014 and palbociclib will be determined. Tmax is the time required after administration for the drug to reach its peak plasma concentration.
Measured: Samples will be collected at prespecified time points up to 12 hours following dosing.
Area under the plasma concentration-time curve from zero to 12 hours (AUC 0-12) for AZD 2014 and palbociclib.
The plasma concentrations of AZD2014 and palbociclib will be determined. Area under the curve is the integral of the concentration-time curve. The area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to drug after administration. The area under the curve is dependent on the rate of elimination of the drug from the body and the dose administered.
Measured: Samples will be collected at prespecified time points up to 12 hours following dosing.
Area under the plasma concentration-time curve from zero to 24 hours (AUC 0-24) for AZD 2014 and palbociclib.
The plasma concentrations of AZD2014 and palbociclib will be determined. Area under the curve is the integral of the concentration-time curve. The area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to drug after administration. The area under the curve is dependent on the rate of elimination of the drug from the body and the dose administered.
Measured: Samples will be collected at prespecified time points up to 24 hours following dosing.
Area under the plasma concentration-time curve from zero to the last measurable concentration (AUC 0-t) for AZD 2014 and palbociclib.
The plasma concentrations of AZD2014 and palbociclib will be determined. Area under the curve is the integral of the concentration-time curve. The area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to drug after administration. The area under the curve is dependent on the rate of elimination of the drug from the body and the dose administered.
Measured: Samples will be collected at prespecified time points up to 9 days following dosing.
Area under the plasma concentration-time curve from zero to infinity (AUC 0-∞) for AZD 2014 and palbociclib.
The plasma concentrations of AZD2014 and palbociclib will be determined. Area under the curve is the integral of the concentration-time curve. The area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to drug after administration. The area under the curve is dependent on the rate of elimination of the drug from the body and the dose administered.
Measured: Samples will be collected at prespecified time points up to 9 days following dosing.
Terminal elimination rate constant (λz) for AZD 2014 and palbociclib.
The plasma concentrations of AZD2014 and palbociclib will be determined. The elimination rate constant is the rate at which drug is cleared from the body assuming first-order elimination
Measured: Samples will be collected at prespecified time points up to 9 days following dosing.
Terminal plasma half-life (t1/2λz) for AZD 2014 and palbociclib.
The plasma concentrations of AZD2014 and palbociclib will be determined. The terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.
Measured: Samples will be collected at prespecified time points up to 9 days following dosing.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2015 (estimated)
- Study start7 Dec 2015
- Primary completion30 Mar 2018
- Study completion23 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced and Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Anja Wiliams, Principal investigator, Sarah Cannon Research Institute UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02599714
- Sponsor's protocol ID
- D2270C00020
- Other IDs
- 264477, 2015-003320-30, 2015
- Acronym
- PASTOR
- Status last verified
- Jun 2024
- First submitted
- 5 Nov 2015
- Last updated
- 6 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Multicenter Study of the Combination of AZD2014 and Palbociclib on a Background of Hormonal Therapy in Patients With Locally Advanced/Metastatic Estrogen Receptor Positive Breast Cancer Comprising a Safety, Pharmacokinetic and Preliminary Efficacy Evaluation Followed by a Randomized, Double-Blind, Placebo-controlled, Parallel Group Extension (PASTOR).
- ClinicalTrials.gov ID
- NCT02599714
- Acronym / sponsor ID
- PASTOR / D2270C00020
- Conditions
- Advanced and Metastatic Breast Cancer
- Keywords
- AZD2014, Palbociclib, Fulvestrant, Hormonal Therapy, Estrogen Receptor Positive, Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 7 Dec 2015 (actual)
- Primary completion
- 30 Mar 2018 (actual)
- Study completion
- 23 Nov 2023 (actual)
- First posted
- 9 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This dose finding/extension study was designed originally to consist of three parts: Part A was intended to identify the MTD of the AZD2014/ palbociclib combination on a background of fulvestrant (referred to as the triplet) in postmenopausal women with locally advanced/ metastatic estrogen receptor positive (ER+) breast cancer. Part B was to further characterize safety, tolerability, PK, and preliminary efficacy in single-arm dose expansion groups. Part C was to be a Phase 2, randomized, double-blind, extension comparing the triplet and doublet combinations. Part C was deleted from the protocol and was not performed.
Detailed description
This dose finding/extension study was designed originally to consist of three parts:
Part A is a Phase 1 triplet-dose finding investigation in 3-6 patients per cohort to determine the maximum tolerated dose (MTD) of the triplet.
Part B is a single arm expansion in approximately 27 patients evaluable for response to define the recommended Phase 2 dose (RP2D).
Part C was intended to investigate the efficacy of the triplet combination at the RP2D in a randomized, double-blind, placebo-controlled, stratified, parallel group extension. Part C was intended to include ER+, locally advanced and/or metastatic breast cancer patients who have progressed following prior non-steroidal aromatase inhibitor (NSAI) endocrine therapy. Patients in Part C were to be randomized to receive either the triplet combination (AZD2014 + palbociclib + fulvestrant) or the doublet (matching AZD2014 placebo + palbociclib + fulvestrant). Patients were to be stratified according to hormone sensitivity, presence of visceral metastases, and prior CDK inhibitor treatment. Part C would have been conducted if indicated by the emerging data.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Triplet Combination (Dose Finding) | Experimental | Drug: AZD2014, Drug: Palbociclib, Drug: FulvestrantPhase 1 triplet dose finding phase in 3-6 patients per cohort - approximately 30 patients depending on emerging data to determine the maximum tolerated dose (MTD) of the triplet. |
| Triplet Combination (Dose Expansion) | Experimental | Drug: AZD2014, Drug: Palbociclib, Drug: FulvestrantAdditional patients will be enrolled at the dose determined in Part A. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Signed and dated written informed consent prior to any mandatory study specific procedures, sampling and analyses.
- Signed and dated written informed consent for tumour biopsies. If the tumour is found not to be safely accessible the biopsy will not be taken. Accessible lesions are defined as those which are biopsiable and amenable to repeat biopsy, unless clinically contraindicated. In this case the patient will remain in the study and there will be no penalty or loss of benefit to the patient and they will not be excluded from other aspects of the study.
- Postmenopausal women aged ≥ 18 years
- Negative pregnancy test prior to dosing and willing to use a highly effective method of contraception for the duration of the study and for 90 days after the last dose of IP if they are under 50 unless they have medically confirmed irreversible premature ovarian failure, bilateral oophorectomy, bilateral salpinectomy, or complete or partial hysterectomy.
- World Health Organisation/Eastern Cooperative Oncology Group (ECOG) performance status of patient is 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks.
Key exclusion criteria (55 listed)
- Prior chemotherapy, biological therapy, radiation therapy, or immunotherapy, androgens, thalidomide, other anticancer agents, investigational drug or corticosteroids within 14 days. Patients who received prior radiotherapy to >= 25% of bone marrow are not eligible independent of when it was received. Patients is not eligible if there are unresolved toxicities from prior therapy > CTCAE grade 1 at the start of study treatment with the exception of alopecia.
- Exposure to potent or moderate inhibitors or inducers of CYP3A4/5, Pgp (MDR1) or BCRP within stated washout periods.
- Exposure to sensitive or narrow therapeutic range substrates of drug transporters OATP1B1, OATP1B3, MATE1 and MATE2K within wash-out period (5 x elimination half-life).
- 4 Exposure to proton pump inhibitors within wash-out period (5 x elimination half-life).
- 5. Previous AZD2014, AZD8055 or other dual mTORC1/2 inhibitor
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD2014Also: vistusertibThe triplet combination will be comprised of AZD2014 + palbociclib + fulvestrant. | Drug | Triplet Combination (Dose Expansion), Triplet Combination (Dose Finding) |
| PalbociclibAlso: Ibrance, PD-0332991cyclin dependent kinase inhibitor | Drug | Triplet Combination (Dose Expansion), Triplet Combination (Dose Finding) |
| FulvestrantAlso: FaslodexFulvestrant hormonal therapy as background | Drug | Triplet Combination (Dose Expansion), Triplet Combination (Dose Finding) |
Primary outcome
Parts A and B: Number of adverse events experienced by patients
Time frame: Approximately 16 months
Safety and tolerability assessed through the incidence of adverse events.
15 secondary outcomes
Part B: Progression Free Survival (PFS)
Time frame: Assessed every 8 weeks for approximately 16 months
Parts A and B: Best Objective Response (BOR)
Time frame: Assessed every 8 weeks for approximately 16 months
Parts A and B: Objective Response Rate (ORR)
Time frame: Assessed every 8 weeks for approximately 16 months
Part B: Duration of Response (DoR)
Time frame: Assessed every 8 weeks for approximately 16 months
Part B: Overall Survival (OS)
Time frame: Approximately 24 months
Part A: Peak plasma concentrations (Cmax) of AZD2014 and palbociclib following single dose
Time frame: Samples for single dose PK will be collected at prespecified time points up to 12 hours following dosing.
Parts A and B: Peak plasma concentrations (Cmax) of AZD2014 and palbociclib following multiple doses
Time frame: Samples will be collected at prespecified time points up to 12 hours following dosing.
Parts A and B: Change from baseline in biomarker H-score
Time frame: 16 months
Time to reach peak plasma concentrations (tmax) for AZD 2014 and palbociclib.
Time frame: Samples will be collected at prespecified time points up to 12 hours following dosing.
Area under the plasma concentration-time curve from zero to 12 hours (AUC 0-12) for AZD 2014 and palbociclib.
Time frame: Samples will be collected at prespecified time points up to 12 hours following dosing.
Area under the plasma concentration-time curve from zero to 24 hours (AUC 0-24) for AZD 2014 and palbociclib.
Time frame: Samples will be collected at prespecified time points up to 24 hours following dosing.
Area under the plasma concentration-time curve from zero to the last measurable concentration (AUC 0-t) for AZD 2014 and palbociclib.
Time frame: Samples will be collected at prespecified time points up to 9 days following dosing.
Area under the plasma concentration-time curve from zero to infinity (AUC 0-∞) for AZD 2014 and palbociclib.
Time frame: Samples will be collected at prespecified time points up to 9 days following dosing.
Terminal elimination rate constant (λz) for AZD 2014 and palbociclib.
Time frame: Samples will be collected at prespecified time points up to 9 days following dosing.
Terminal plasma half-life (t1/2λz) for AZD 2014 and palbociclib.
Time frame: Samples will be collected at prespecified time points up to 9 days following dosing.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2024.
- Redacted CSR synopsisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anja Wiliams principal investigator
Sarah Cannon Research Institute UK
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD2014, Palbociclib and Fulvestrant in people with Advanced and Metastatic Breast Cancer, run by AstraZeneca at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 55 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Parts A and B: Number of adverse events experienced by patients (time frame: Approximately 16 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2024.